This project represents an investigation of the effects of induced hyperthermia on mammalian development. We will determine the effects of hyperthermia during critical periods of prenatal and early postnatal development focusing our attention on the production of birth defects and the perturbation of biochemical systems associated with growth and cellular proliferation. Hyperthermia will be induced in guinea pigs and in rats by two methods - by increasing the ambient temperature and by the injection of a bacterial pyrogen. Preliminary experiments have demonstrated that perinatal hyperthermia causes profound disaggregation of brain polyribosomes, dramatic increase on brain amino acid levels and a precipitous fall in plasma levels of triglycerides. We will extend these observations with a detailed study of protein synthesis and phosphorylation and of specialized growth-related biochemical systems. We will attempt to devise model therapies designed to protect the developing fetus from birth defects attributable to fever during the prenatal period and also determine if the mechanisms involved can be exploited to increase the susceptibility of rapidly proliferating cells to hyperthermia an potentially useful agent in cancer chemotherapy.